clinical study of cord blood-derived il-10 cd19-car nk in the treatment of refractory/relapsed b-cell nhl

Conditions: B-cell Non Hodgkin Lymphoma

Summary: to study the safety and effectiveness of cord blood-derived il-10 cd19-car nk in patients with b-cell non-hodgkin's lymphoma

this is an open, single-arm, single-dose, dose-escalation clinical trial designed to evaluate the safety and the preliminary efficacy of cb il-10 cd19-car nk cells. 6-24 patients are planned to be enrolled in the dose-escalation trial (2×10\^6 cells/kg, 3×10\^6 cells/kg, 4×10\^6 cells/kg). the primary endpoints are dlt and mtd; the second is the overall response rates (cr and pr), survival, and progression-free survival. patients will be infused on day 0, day 3, and day 6， respectively.

Eligibility criteria:
inclusion criteria: 1. volunteer to participate in this study and sign an informed consent form; 2. age 18-75 years old, no gender limit; 3. histologically diagnosed as diffuse large b-cell lymphoma (dlbcl), transforming follicular lymphoma (tfl), primary mediastinal b-cell lymphoma (pmbcl), mantle cell lymphoma (mcl) and other inert b-cells nhl conversion type:(1) refractory or relapsed dlbcl refers to the failure to achieve complete remission after 2-line treatment; disease progression during any treatment, or disease stable time equal to or less than 6 months; or disease progression or recurrence within 12 months after autologous hematopoietic stem cell transplantation ； (2) refractory or relapsed mcl must be resistant to or intolerable to btk inhibitors; (3) refractory or relapsed indolent b-cell nhl is the failure or recurrence of third-line treatment; (4) previous treatment must include cd20 monoclonal antibody treatment (unless the subject is cd20 negative) and anthracyclines; 4. at least one measurable lesion with the longest diameter ≥ 1.5 cm exists; 5. the expected survival period is ≥12 weeks; 6. the puncture section of the tumor tissue was positive for cd19 expression; 7, ecog score 0-2 points; 7. sufficient organ function reserve: (1) alanine aminotransferase, aspartate aminotransferase ≤ 2.5× unl (upper limit of normal value); (2) creatinine clearance rate (cockcroft-gault method) ≥60 ml/min; (3) serum total bilirubin and alkaline phosphatase ≤1.5× unl; （4）glomerular filtration rate\>50ml/min cardiac ejection fraction (ef) ≥50%; (5) under natural indoor air environment, basic oxygen saturation\>92% . 8. allow a previous stem cell transplantation. 9. the approved anti-b-cell lymphoma treatments, such as systemic chemotherapy, systemic radiotherapy, and immunotherapy, have been completed for at least 3 weeks before the study medication; 10. allow patients who have previously received car-t cell therapy and have failed or relapsed after 3 months of evaluation; 11. female subjects of childbearing age must have a negative pregnancy test and agree to take effective contraceptive measures during the trial. 12. two tests for the new coronavirus were negative. exclusion criteria: 1. those who have a history of allergies to any of the ingredients in cell products; 2. history of other tumors; 3. previously presented with ii-iv degree (glucksberg criteria) acute gvhd or extensive chronic gvhd; or are receiving anti-gvhd treatment; 4. have received gene therapy in the past 3 months; 5. active infections that require treatment (except for simple urinary tract infections and bacterial pharyngitis), but preventive antibiotics, antiviral and antifungal infection treatments are allowed; 6. hepatitis b (hbsag positive, but hbv-dna \<103 is not an exclusion criterion) or hepatitis c virus infection (including virus carriers), syphilis and other subjects with acquired and congenital immunodeficiency diseases, including but not limited to people living with hiv; 7. according to the new york heart association's heart function classification standard, it is classified as grade iii or grade iv impaired subjects; 8. those who have received anti-tumor therapy in the early stage but the toxic reaction has not recovered (the ctcae 5.0 toxic reaction has not recovered to ≤1, except for fatigue, anorexia, and hair loss); 9. subjects with a history of epilepsy or other central nervous system diseases; 10. enhanced ct or mri of the head showed evidence of central nervous system lymphoma; 11. have any other drugs that target cd19; 12. women who are breastfeeding and unwilling to stop breastfeeding; 13. any other situation that the investigator believes may increase the subject's risk or interfere with the test results.